User:Queensarms0/sandbox

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File:MOD binding.png

Modulation[edit]

Modifiers bind with Cys-Loop receptors in the following three sites within the transmembrane domain: in one subunit, between adjacent subunits, and in the center of the pentameric pore formation[1]. The binding of these modifiers affects varying receptor functions involved in physiological learning and memory, neurological disorders, and drug targeting[2]. This effect depends on the type of modification (phosphorylation, fatty acid, or cannabinoid (CB)) and the type of receptor.

nAChR[edit]

nACh receptors are found commonly on presynaptic terminals, cell bodies, dendrites of neuronal subtypes[3], glia, blood cells, keratinocytes, endothelial cells, and multiple digestive system and lung cells[4]. They normally function in sensing pain, sleep patterns, appetite, learning, mental rewards systems, regulating synaptic transmission and plasticity[5], memory, autonomous action, and neuromuscular relaxation[6]. Phosphorylation of nAChRs relates to nicotine addiction, Alzheimer's Disease, and schizophrenia[7]. Unsaturated fatty acids (linoleic and linolenic) potentiate nAChRs function while endogenous cannabinoids, specifically arachidonic acid (AA) provide inhibitory negative feedback. An AA derivative, Anandamide (AEA) directly interacts with the receptor in a reversible and non-competitive manner[8].

GABAAR[edit]

GABAA receptors are found throughout the central nervous system[9]. They normally function in major anesthetic actions[10] and are essential for maintaining hormonal neurotransmission in the brain[11]. They are a common target for therapeutic drugs, including barbituates, steroids, anesthetics, benzodiazapine, alcohols, and picrotoxin[12][13]. Phosphoylation of GABAAR is involved in epilepsy, anxiety, forms of addiction, and anaesthesia[14]. Fatty acids inhibit function (linoleic acid inhibits in a concentration dependent manner), and while AA inhibit as well, AEA has no effect[15].

GlyR[edit]

Gly receptors are found in the central nervous system, particularly within the brain stem and spinal cord[16][17]. They normally function in regulating pain, respiration, motor function, development, and reward systems[18]. Phosphorylation correlates to chronic inflammatory pain[19], and alkaloid strychnine acts as a competitive antagonist, causing agitation, muscle spasms, and convulsions[20]. Δ9-tetrahydrocannabinol (THC) potentiates GlyR along with AEA and other cannabinoids, releasing dopamine, which is involved in drug addiction[21].

5-HT3[edit]

5-HT3 receptors are found in both postsynaptic and presynaptic neurons of the central and peripheral nervous systems, primarily in the brain stem. They normally function in neurotransmitter release, rewards systems, anxiety, psychosis, nociception, cognitive function, sensory processing, cardiovascular regulation, and gut function[22][23]. They are inhibited by AEA and THC, inducing antinociceptince, antiemetic effects, and irritable bowel syndrome[24].

  1. ^ Stuart A. Forman, Keith W. Miller. “Anesthetic Sites and Allosteric Mechanism of Action on Cys-Loop Ligand-gated Ion Channels” Can J Anaesth. 2011 February; 58(2): 191–205. doi:10.1007/s12630-010-9419-9.
  2. ^ Cecilia Bouzat. “New insights into the structural bases of activation of Cys-loop receptors” Journal of Physiology. 0928-4257/$ - see front matter 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.jphysparis.2011.09.012
  3. ^ Li Zhang, Wei Xiong. “Modulation of the Cys-Loop Ligand-gated Ion Channels by Fatty Acid and Cannabinoids. Vitamins and Hormones, Volume 81. ISSN 0083-6729, DOI: 10.1016/S0083-6729(09)81012-1
  4. ^ Cecilia Bouzat. “New insights into the structural bases of activation of Cys-loop receptors” Journal of Physiology. 0928-4257/$ - see front matter 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.jphysparis.2011.09.012
  5. ^ Li Zhang, Wei Xiong. “Modulation of the Cys-Loop Ligand-gated Ion Channels by Fatty Acid and Cannabinoids. Vitamins and Hormones, Volume 81. ISSN 0083-6729, DOI: 10.1016/S0083-6729(09)81012-1
  6. ^ Stuart A. Forman, Keith W. Miller. “Anesthetic Sites and Allosteric Mechanism of Action on Cys-Loop Ligand-gated Ion Channels” Can J Anaesth. 2011 February; 58(2): 191–205. doi:10.1007/s12630-010-9419-9.
  7. ^ Sahil Talwar, Joseph W. Lynch. “Phosphorylation mediated structural and functional changes in pentameric ligand-gated ion channels: Implications for drug discovery.” The International Journal of Biochemistry & Cell Biology. [1] 1357-2725/© 2014 Elsevier Ltd.
  8. ^ Li Zhang, Wei Xiong. “Modulation of the Cys-Loop Ligand-gated Ion Channels by Fatty Acid and Cannabinoids. Vitamins and Hormones, Volume 81. ISSN 0083-6729, DOI: 10.1016/S0083-6729(09)81012-1
  9. ^ Cecilia Bouzat. “New insights into the structural bases of activation of Cys-loop receptors” Journal of Physiology. 0928-4257/$ - see front matter 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.jphysparis.2011.09.012
  10. ^ Stuart A. Forman, Keith W. Miller. “Anesthetic Sites and Allosteric Mechanism of Action on Cys-Loop Ligand-gated Ion Channels” Can J Anaesth. 2011 February; 58(2): 191–205. doi:10.1007/s12630-010-9419-9.
  11. ^ Li Zhang, Wei Xiong. “Modulation of the Cys-Loop Ligand-gated Ion Channels by Fatty Acid and Cannabinoids. Vitamins and Hormones, Volume 81. ISSN 0083-6729, DOI: 10.1016/S0083-6729(09)81012-1
  12. ^ Li Zhang, Wei Xiong. “Modulation of the Cys-Loop Ligand-gated Ion Channels by Fatty Acid and Cannabinoids. Vitamins and Hormones, Volume 81. ISSN 0083-6729, DOI: 10.1016/S0083-6729(09)81012-1
  13. ^ Cecilia Bouzat. “New insights into the structural bases of activation of Cys-loop receptors” Journal of Physiology. 0928-4257/$ - see front matter 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.jphysparis.2011.09.012
  14. ^ Sahil Talwar, Joseph W. Lynch. “Phosphorylation mediated structural and functional changes in pentameric ligand-gated ion channels: Implications for drug discovery.” The International Journal of Biochemistry & Cell Biology. [2] 1357-2725/© 2014 Elsevier Ltd.
  15. ^ Li Zhang, Wei Xiong. “Modulation of the Cys-Loop Ligand-gated Ion Channels by Fatty Acid and Cannabinoids. Vitamins and Hormones, Volume 81. ISSN 0083-6729, DOI: 10.1016/S0083-6729(09)81012-1
  16. ^ Li Zhang, Wei Xiong. “Modulation of the Cys-Loop Ligand-gated Ion Channels by Fatty Acid and Cannabinoids. Vitamins and Hormones, Volume 81. ISSN 0083-6729, DOI: 10.1016/S0083-6729(09)81012-1
  17. ^ Cecilia Bouzat. “New insights into the structural bases of activation of Cys-loop receptors” Journal of Physiology. 0928-4257/$ - see front matter 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.jphysparis.2011.09.012
  18. ^ Li Zhang, Wei Xiong. “Modulation of the Cys-Loop Ligand-gated Ion Channels by Fatty Acid and Cannabinoids. Vitamins and Hormones, Volume 81. ISSN 0083-6729, DOI: 10.1016/S0083-6729(09)81012-1
  19. ^ Sahil Talwar, Joseph W. Lynch. “Phosphorylation mediated structural and functional changes in pentameric ligand-gated ion channels: Implications for drug discovery.” The International Journal of Biochemistry & Cell Biology. [3] 1357-2725/© 2014 Elsevier Ltd.
  20. ^ Cecilia Bouzat. “New insights into the structural bases of activation of Cys-loop receptors” Journal of Physiology. 0928-4257/$ - see front matter 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.jphysparis.2011.09.012
  21. ^ Li Zhang, Wei Xiong. “Modulation of the Cys-Loop Ligand-gated Ion Channels by Fatty Acid and Cannabinoids. Vitamins and Hormones, Volume 81. ISSN 0083-6729, DOI: 10.1016/S0083-6729(09)81012-1
  22. ^ Li Zhang, Wei Xiong. “Modulation of the Cys-Loop Ligand-gated Ion Channels by Fatty Acid and Cannabinoids. Vitamins and Hormones, Volume 81. ISSN 0083-6729, DOI: 10.1016/S0083-6729(09)81012-1
  23. ^ Cecilia Bouzat. “New insights into the structural bases of activation of Cys-loop receptors” Journal of Physiology. 0928-4257/$ - see front matter 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.jphysparis.2011.09.012
  24. ^ Li Zhang, Wei Xiong. “Modulation of the Cys-Loop Ligand-gated Ion Channels by Fatty Acid and Cannabinoids. Vitamins and Hormones, Volume 81. ISSN 0083-6729, DOI: 10.1016/S0083-6729(09)81012-1
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